It has previously been established that genes such as recA are involved in recombination in bacteria, which contributes to intra- and intergenic variation. intragenic variation is thought to be important for bacterial growth. Bacterial RecA proteins are important in recombinational repair of damages DNA, in bacterial response to environmental stress (e.g., SOS), and also in functions such as DNA transformation and chromosomal rearrangement that are involves in bacterial pathogenesis. Nothing is known of the existence or role of recombinase in H. pylori, and no H. pylori recA gene has been identified.
Helicobacter pylori is the major causative agent of chronic superficial gastritis in humans, and infection with this organism is an important etiologic factor in the pathogenesis of peptic ulcer disease and possibly gastric cancer (20-22). In terms of human suffering and financial burden, H. pylori infection is very costly. There is no vaccine or fully effective treatment for H. pylori infection.
Thus there exists a need for a vaccine against H. pylori infection. Such a vaccine, if comprising a live attenuated bacterium should not be susceptible to reversion to the wild type. The present invention meets this need by providing the H. pylori recA gene and a strain of H. pylori that has been genetically altered so that no functional recombinase is produced.
SUMMARY OF THE INVENTION
An isolated nucleic acid encoding the Helicobacter pylori recombinase comprising the nucleotide sequence defined in the Sequence Listing as SEQ ID NO:1 is provided. Also provided is an isolated nucleic acid that selectively hybridizes with the nucleic acid of claim 1 under stringent conditions and is at least 70% complementary with the segment and strand of the nucleic acid of SEQ ID NO:1 to which it hybridizes. The recombinase-encoding nucleic acid and selectively hybridizing nucleic acids of the invention can be in a vector suitable for expressing the nucleic acid. The nucleic acid in a vector can be in a host suitable for expressing the nucleic acid.
Having discovered the existence of a recombinase in H. pylori, the invention also provides a mutant strain of H. pylori that does not express a functional recombinase (recA.sup.- mutant). The mutant can either not express recombinase or express a non-functioning recombinase. The recA.sup.- mutants are more sensitive to acidic pH than are the wild-type H. pylori. Thus, the invention provides a method of inducing acid sensitivity in H. pylori, comprising mutating the H. pylori so that it does not express a functional recombinase, the absence of a functioning recombinase resulting in increased acid sensitivity.
An immunogenic amount of the recA.sup.- mutant H. pylori in a pharmaceutically acceptable carrier can be used as a vaccine. A method of immunizing a subject against infection by H. pylori comprises administering to the subject an immunogenic amount of mutant H. pylori in a carrier for the mutant.